The Impact of Gene Polymorphisms on the Success of Anticholinergic Treatment in Children with Overactive Bladder

Abstract

Aim. To determine the impact of gene polymorphisms on detrusor contraction-relaxation harmony in children with lower urinary tract symptoms (LUTS). Materials and Methods. Toilet trained children older than 5 years of age with LUTS and normal neurological examination underwent videourodynamic study. The control group was composed of age matched children with no voiding complaints. The study group who filled out the voiding dysfunction symptom score before and after the treatment received standard oxybutynin treatment and was reevaluated 1 year after treatment. Genomic DNA was isolated from all patients and subjected to PCR for amplification. Genotyping of ARGHEF10, ROCK2, ADRB3, and CYP3A4 was carried out with Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) method. Results. 34 (45%) and 42 (55%) patients were enrolled in the study and control group, respectively. ARGEF10 GG, ADRB3 TC, and CYP3A4 AG genotype patients displayed insignificant difference between pre- and posttreatment voiding dysfunction symptom score and bladder volumes. Conclusions. The polymorphism of genes in the cholinergic pathway did not significantly differ clinical parameters. On the other hand, polymorphic patients in the adrenergic pathway seemed to suffer from clinical disappointment. For this reason, we think that the neglected adrenergic pathway could be a new therapeutic target for the treatment of anticholinergic resistant LUTS in children.

Role of β‐3 adrenergic receptor polymorphism in overactive bladder

“…Our study did not find differences between genotypes and anticholinergic medication failure. As mentioned previously, the β‐3 receptor is implicated in inhibition of cholinergic nerve signals in vitro and more recently this was suggested by work in vivo . Gurocak and colleagues studied 34 children with lower urinary tract symptoms.…”

“…As mentioned previously, the β-3 receptor is implicated in inhibition of cholinergic nerve signals in vitro and more recently this was suggested by work in vivo. 8,10 Gurocak and colleagues studied 34 children with lower urinary tract symptoms. As compared to those with the wild type genotype, those with the variant genotype of the rs4994 SNP were less likely to improve with anticholinergic medication therapy.…”

Vascular endothelial growth factor as an angiogenesis biomarker for the progression of autosomal dominant polycystic kidney disease

“…The identification of SNPs is a new means to study the etiology of polygenetic disorders with complex inheritance patterns (Gurocak et al, 2015). ADPKD may progress to a stage where there is a need for hemodialysis and/or kidney transplant, and is influenced by modifier genes (Obeidova et al, 2014).…”

Rho‐kinase Gene Polymorphisms in Related Disease States

“…Gurocak et al [38] found that genotype and allele frequencies were not signiicantly diferent between the children with overactive bladder and the control group for ROCK2 gene rs2230774 (Thr431Asn) polymorphism. It was concluded that this polymorphism has no impact on the response to anticholinergic treatment.…”

“…The Thr431Asn polymorphism lies immediately carboxyl-terminal to the start of the putative coiled-coil region and encodes an amino acid substitution in the predicted coiled-coil domain of the protein, which is associated with ROCK2/ROCK2 parallel homodimerization Cardiac septal defects rs2230774 (Thr431Asn) [26] Systemic sclerosis rs10178332 [28] rs2230774 (Thr431Ser), rs2230774 (Thr431Asn), rs35768389 (Asp601Val), rs726843, rs2290156, rs965665, rs6755196, rs10929732 [28] Behçet's disease rs35768389 (Asp601Val), rs1515219 [29] rs726843, rs2290156, rs965665, rs10178332, rs2230774, rs6755196, rs10929732, rs34945852 [29] Rheumatoid arthritis rs1868584 [23] Diabetic retinopathy rs2230774 (Thr431Asn), rs1130757 (Arg83Lys) [31] Primary open-angle glaucoma rs2290156, rs965665, rs10178332, rs2230774 (Thr431Asn), rs2230774 (Thr431Ser), rs6755196, rs726843 [32] Ischemic stroke rs921322, rs8996, rs6753921, rs2230774, rs1515219, rs6716817, rs10203916, rs6755337, rs12622447 [33] Obesity-related metabolic syndrome rs2230774 (Thr431Asn) [34] rs2230774 (Thr431Ser), rs726843, rs2290156, rs965665, rs10178332, rs6755196 [34] Respiratory distress syndrome rs726843, rs2290156, rs10178332, rs35768389 (Asp601Val) [35] rs1515219, rs965665, rs2230774 (Thr431Asn), rs6755196, rs10929732 [35] Chronic kidney disease rs2230774 (Thr431Asn) [36] Urinary albumin excretion rs1515219, rs2290156 [37] Overactive bladder rs2230774 (Thr431Asn) [38] Idiopathic generalized epilepsy rs2230774 (Thr431Asn) [39] Migraine rs2230774 (Thr431Asn) [40] Diabetes rs1868584 (with type-1 diabetes)…”